Table 2. Gene Prioritization by Mutation Burden Analysis.
Mutation burden analysis was conducted for 112 genes with biological relevance to AVSD. The top 6 ranked genes are shown.
| GENE | CASES n = 81 |
CONTROLS n = 4300* |
Odds Ratio | 95% Confidence Interval | Fisher’s Exact p-value (two-tailed) |
Fisher’s Exact p-value with nucleotide-by- nucleotide coverage correction+ | |||
|---|---|---|---|---|---|---|---|---|---|
| With Mutation | Without Mutation | With Mutation | Without Mutation | ||||||
| NIPBL |
Rare Rare Damaging |
6 3 |
75 78 |
102 27 |
4198 4273 |
3.3 6.1 |
1.1 – 7.8 1.2 – 20.4 |
0.02 0.008 |
0.01 0.02 |
| CHD7 |
Rare Rare Damaging |
9 3 |
72 78 |
215 58 |
3940 4097 |
2.3 2.7 |
1.0 – 4.7 0.5 – 8.6 |
0.04 0.02 |
0.07 0.3 |
| CEP152 |
Rare Rare Damaging |
8 4 |
73 77 |
178 70 |
3925 4033 |
2.4 3.0 |
1.0 – 5.1 0.7 – 8.3 |
0.03 0.08 |
0.03 0.05 |
| BMPR1a |
Rare Rare Damaging |
3 3 |
78 78 |
31 27 |
4269 4273 |
5.3 6.1 |
1.0 – 17.5 1.2 – 20.4 |
0.02 0.008 |
0.02 0.02 |
| ZFPM2 |
Rare Rare Damaging |
11 8 |
70 73 |
282 189 |
3872 3965 |
2.2 2.3 |
1.0 – 4.2 0.9 – 4.9 |
0.03 0.05 |
0.03 0.05 |
| MDM4 |
Rare Rare Damaging |
6 6 |
75 75 |
68 53 |
4232 4247 |
5.0 6.4 |
1.7 – 11.9 2.2 – 15.2 |
3.2 x 10-4 1.8 x 10-5 |
0.002 6.8 x 10-4 |
*
The EVS does not provide sample level information, therefore for consistency the burden analysis assumes that each genotype serves as an independent sample. The total number of patients for the EVS cohort per gene was the median of the total number at each position with a rare variant in that gene.
+
Refer to Table 3 for variant level data